CASE STUDY:OPTIMIZING SITE AND PATIENT ENGAGEMENT IN RESCUE STUDIES

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Last Update: 17022020

THE CASE A Phase II oncology study run by a large CRO struggled with slow patient recruitment, poor site engagement, and data entry delays

THE FACTS Sponsor: Small U.S. biotech with <100 employeesStudy Location: United States

PR

E-R

ESC

UE

P

OST

-RE

SCU

E

THE RESULT:Worldwide Clinical Trials engaged sites to dramatically boost recruitment and improve data entry, allowing the sponsor to hit recruitment targets and database lock on schedule.

The sponsor has since awarded two additional pivotal Phase III studies for this product to Worldwide Clinical Trials.

ACTIVE SITES RECRUITMENTSCREENINGS PER MONTH

DATA MANAGEMENT

19

24

80%

100%

8.3

19.5

Significantly behind schedule:

37 patients enrolled in 7 months

Exceeded recruitment target on time:

56 patients enrolled in 4 months

(Total 93 recruited, of 90 needed)

Delayed data entry compromised

data integrity and primary end point

management

On-time database lock, with interim analysis on key data completed

in 3 weeks

Last Update: 10062020

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SPONSOR FACED 3 CHALLENGES

PATIENT RECRUITMENT & RETENTIONThe study began in Q3 2018. At the time of rescue from a large CRO in Q2 2019, the study had 80% of sites activated but was far behind on enrollment. This can be caused by lack of site engagement, improper recruitment techniques, and a poor understanding of the patient population and their journey.

SITE MANAGEMENTThe sponsor felt sites were not being closely managed and approached when start-up was slow. This can reflect one-size-fits-all planning for site engagement or ineffective communication strategies. Worldwide needed to re-engage 15 sites that were not currently recruiting.

DATA MANAGEMENTData were not entered promptly, even for the primary end point. This can result from poor site understanding of the importance of timely data collection, lack of training in study data systems, ineffective site communication with patients, and complex data entry processes. The sponsor needed help gaining control of the integrity of the data.

The sponsor selected Worldwide Clinical Trials to take over the study from a large CRO.

Last Update: 10062020

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WORLDWIDE’S RESCUE SOLUTIONSWhen it’s decided that a project needs to be rescued, it’s critically important that intervention is swift to keep the study on time and ensure quality. Worldwide used a flexible and customized approach to collaborate closely with the sponsor and get the study back on track. Three key strategies included:

Worldwide focused on understanding the patient

pathway to best support patient recruitment efforts. This included

working with stakeholders to understand key inclusion criteria, severity scales, visit schedules,

and how best to reach the patients and their families.

Worldwide also shortened the screening period, easing the site

and patient burden.

Frequent communication with site staff and

physicians, in addition to regular site education

and extra outreach when needed, improved

site engagement and recruitment for the study.

The Worldwide team manually reviewed data

compliance daily in preparation for the study’s

interim analysis. This helped justify the initiation of a

Phase III efficacy program and support the product for

commercialization.

Increase the Focus on Patients

Partnering Closely with Sites

Detailed Data Review

CRO TRANSITION:It can be intimidating to contemplate a shift in CRO midstream. But even the most complex, struggling studies have a chance to succeed when a competent, uncommon CRO takes the reins.

• Worldwide completed the CRO transition seamlessly in less than 90 days and in the interim, conducted feasibility and activated 4 more high-impact sites.

• Worldwide’s study rescue allowed the sponsor to take a step back and focus on their strategy for further product development.

Last Update: 10062020

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30

25

20

15

10

5

0

Nov-18

10

Sep-18

20

Oct-18

0

12

Dec-18

1

10

Feb-19

310

Mar-19

1011

Sep-19

23

13

July-19

17

11

Aug-19

22

8

Jan-19

64

Jun-19

16

8

Apr-19

88

May-19

15

7

THE RESULT: A SUCCESSFUL RESCUE

PATIENT RECRUITMENT & RETENTION:Worldwide fully enrolled the study on time, with 93 patients within 7 months of the CRO transition. This more than doubled the prior recruitment rate, and the average number of patients screened tripled between August and September.

DATABASE LOCK: The program achieved DBL on schedule, with interim analysis on “key” data points completed within 3 weeks. Worldwide was able to recruit for the study, manage all vendors, and bring in the data needed for an end-of-Phase II meeting with the FDA.

TOTAL PATIENTS SCREENED AND RANDOMIZED PER MONTH

Interactive response technology (IRT) Bioanalytics lab

eDiary

Electronic data capture (eDC)

Central lab

Central IRB

EXTERNAL VENDORS

MANAGED BY WORLDWIDE

FORWARD DEVELOPMENT PROGRESS: The sponsor has awarded two pivotal Phase III studies for this drug/indication to Worldwide and has begun discussions for a pivotal study on another drug in their pipeline.

Screened Randomized

Worldwide transitioned as primary CRO here

Last Update: 10062020

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COMMON ONCOLOGY TRIAL CHALLENGES—AND HOW TO ADDRESS THEM

RECRUITMENT CHALLENGES VARY BY STUDY. In this case, recruiting relatively stable patients who were doing well on an approved prostate cancer maintenance therapy was difficult—they didn’t tend to complain of the symptoms required for eligibility. This made it hard for healthcare staff to identify them and made patients unlikely to seek a trial or care on their own.

• Recruitment techniques should be customized to meet the needs of the study and its target population. This requires a deep understanding of the patient journey and a creative, tailored approach to both find and approach patients with a study that meets their needs.

1

PAIN POINTS REQUIRE HANDS-ON MANAGEMENT. Many studies struggle with compliance either among patients or study staff. In this case, patients were not sufficiently reporting symptoms—required as part of the primary end point—in the electronic diary. This disrupted the timeline and jeopardized data integrity.

• Devote extra time and attention to managing compliance-related pain points. This may involve daily check-ins and repeated reminders about the importance of compliance. Extra monitoring can avoid the higher price of a failed study.

2

SITE ENGAGEMENT MAKES A BIG DIFFERENCE. A major reason this case suffered from slow recruitment and poor compliance was due to inadequately engaged sites. Loss of interest and poor morale only compound recruitment challenges, and the cycle can lead to a downward spiral in study metrics.

• Ensure ongoing site engagement based on site-specific needs. Some site staff get discouraged when initial efforts do not lead to good recruitment, while others may see certain trial requirements as a nuisance. By identifying site-specific issues, CROs and sponsors can tailor engagement strategies throughout the life of the study.

3

The takeaways from this successful study rescue can be used to refine approaches to many study rescues and can benefit any planning team during trial design and implementation.

Last Update: 10062020

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Worldwide Clinical Trials was chosen to take over an active Phase II clinical trial from a large CRO in prostate cancer patients experiencing hot flash symptoms. The sponsor came to Worldwide because they felt that site engagement was weak, recruitment was not meeting timelines, and data entry was behind. The study had been running for about 9 months, and it

was clear that the existing approach had failed.

We took over the study with more hands-on tactics, broader site management, and regular education and communication. We understood the patient pathway and drove the operational execution more directly.

This approach turned most ambivalent sites into active recruiters, more than doubling the recruitment rate in the first 3 months and tripling that rate in the following 3 months. Enrollment closed on schedule. The Worldwide team’s flexible commitment throughout the study rescue process allowed for accurate, complete and verifiable data to support the initiation of a Phase III efficacy program.

The success of our rescue efforts resulted in expanded collaboration on other products in the sponsor’s pipeline, as well as a growing, trust-based relationship. This is our goal with every study rescue—to work with the sponsor to enable timely study solutions and create opportunities for them to successfully pursue further drug development.

Katie HurleySenior Project ManagerWorldwide Clinical Trials

A WORD FROM THE PROJECT MANAGER

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SERVICES WITH WORLDWIDE• Site Start-Up

• Project Management

• Data Management

• Clinical

• Pharmacovigilance

• Medical Monitoring

• Quality Assurance

• Medical Writing

Last Update: 10062020

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Rebecca Eskew Executive Director, Project Management, Oncology and HematologyRebecca has worked in clinical research for over 20 years, joining Worldwide Clinical Trials in May 2019 as a therapeutic and operational advisor for oncology and rare indications. She began her career in research as an in-house CRA for a large, global CRO and then moved into a regional CRA role for the same company. Rebecca was promoted to project management and led a Phase III global pivotal program, which resulted in successful FDA and EMEA registration for a product to treat chronic lymphocytic leukemia.

Rebecca has approximately 15 years of experience in oncology, Phases I through III, including first-in-human trials. She has led or overseen trials of several first-in-class compounds, including CAR-T therapies and other immuno-oncology drugs. She has participated in regulatory inspections and has been part of four successful BLA submissions and subsequent FDA and EMEA approval for new immuno-oncology products. She has experience writing protocols and safety summaries, INDs, and CSRs. She was most recently the head of clinical operations for a small biotechnology company focused in CAR-T (both autologous and allogeneic) and bispecific therapies. In this role, she was responsible for all clinical operations activities, including liaising with the manufacturing team to ensure on-time delivery of patient T-cell products. Rebecca has experience with autologous, non-engineered T-cell therapy, autologous engineered T-cell therapies, and allogeneic T-cell therapies. Rebecca has a Bachelor of Science degree in zoology/pre-medicine from The University of Oklahoma and is in pursuit of her Master of Science degree.

THERE’S NO SUBSTITUTE FOR UNCOMMON EXPERTISE MEET YOUR PARTNERS

Mireille Cantarini, BSc, MB ChB, MRCP, FFPM Senior Medical Director, Medical AffairsDr. Cantarini brings a long history in clinical research to her role as medical and scientific affairs consultant at Worldwide. Sponsors focused on oncology appreciate her experience with the Oncology Early Clinical Development organization at AstraZeneca, where she was involved in Phase I/IIb studies in several cancer indications across global locations (including the EU, US, Southeast Asia, Japan, South America, South Africa, and China). Most recently, Dr. Cantarini was involved as Executive Medical Director in the Osimertinib (indication T790M-positive non-small cell lung cancer (NSCLC)) program, taking the clinical development from first dose-in-human to full regulatory approvals in all major territories (FDA, EMEA, Japan, and China) in four years. She has been board certified in Pharmaceutical Medicine (GMC specialist register) since 2005 and has a 30-plus-year record of publications in peer-reviewed journals.

Gaurav Sharma, M.Pharm, PMP, C.Sci, FIBMS, MICR Senior Vice President, Project Management, OncologyGaurav is a strategic and tactical operations leader, with a wealth of experience building and managing high-performing teams and developing innovative, creative, and quality-driven solutions for clients. Gaurav brings strong and varied therapeutic expertise and strategic leadership skills, developed across franchise areas within several CROs and now to Worldwide. Prior to joining Worldwide, Gaurav was a Senior Vice President and Head of Global Project Management with Premier Research. More recently, Gaurav was responsible for overall successful delivery of clinical programs involving immune checkpoint inhibitors for the treatment of solid tumors and hematological malignancies.

Gaurav has also worked extensively in acute myeloid leukemia, cutaneous T-cell lymphoma and prostate cancer. He was program director for a large program with tyrosine kinase inhibitor (TKI) involving several studies, including pivotal study for patients with EGFR mutated NSCLC, leading to marketing authorization. Gaurav is a Project Management Institute (PMI) certified Project Management Professional, a Certified Director by the World Council for Corporate Governance and a Chartered Scientist (C.Sci) by the Science Council in the United Kingdom, with a wealth of experience working with pharmaceutical companies, such as Lundbeck, Allergan, Takeda, and global CROs, such as IQVIA, Parexel, Icon, Premier Research, and ClinTec.

Last Update: 10062020

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